Control of developmental regulator's by polycomb in human embryonic stem cells
Control of developmental regulator's by polycomb in human embryonic stem cells
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DOI：
10.1016/j.cell.2006.02.043
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发表时间：
2006-04-21
期刊：
影响因子：
64.5
通讯作者：
Young, RA
中科院分区：
文献类型：
--
作者：
Lee, TI;Jenner, RG;Young, RA
Polycomb组蛋白对于后生动物的早期发展至关重要，但是他们对人类发展的贡献尚不清楚。我们在人类胚胎茎（ES）细胞中的整个非重复部分中绘制了PolyComb抑制复合物2（PRC2）亚基Suz12。我们发现Suz12分布在编码关键发育调节器的200多个基因的大部分中。这些基因在组蛋白H3K27处三甲基化的核小体占据，被转录抑制，并包含基因组中一些最高度保守的非编码元件。我们发现，在ES细胞分化过程中，PRC2靶基因优先激活，ES细胞调节剂Oct4，Sox2和Nanog coococupy是这些基因的显着子集。这些结果表明，PRC2在ES细胞中占据了一组特殊的发育基因，必须抑制以维持多能性，并且在ES细胞分化过程中有助于激活。
Polycomb group proteins are essential for early development in metazoans, but their contributions to human development are not well understood. We have mapped the Polycomb Repressive Complex 2 (PRC2) subunit SUZ12 across the entire nonrepeat portion of the genome in human embryonic stem (ES) cells. We found that SUZ12 is distributed across large portions of over two hundred genes encoding key developmental regulators. These genes are occupied by nucleosomes trimethylated at histone H3K27, are transcriptionally repressed, and contain some of the most highly conserved noncoding elements in the genome. We found that PRC2 target genes are preferentially activated during ES cell differentiation and that the ES cell regulators OCT4, SOX2, and NANOG cooccupy a significant subset of these genes. These results indicate that PRC2 occupies a special set of developmental genes in ES cells that must be repressed to maintain pluripotency and that are poised for activation during ES cell differentiation.